Substance P Acetate

The tachykinin, substance P (SP), affects eosinophil function by direct and indirect mechanisms and has been shown to cause equine eosinophils to adhere to vascular endothelium and to release cytokines that increase cell adherence. The aim of this study was to determine whether SP could act directly on equine eosinophils in vitro. Eosinophil activation was also compared in cells from normal ponies and those with insect hypersensitivity as SP may be released in the skin of hypersensitive animals. SP caused equine eosinophils to adhere, migrate and produce superoxide, although high concentrations were required to produce these effects [10 +/- 2% adherence, 45 +/- 20 cells/0.3 mm2 and 48 +/- 7 nmol (of reduced cytochrome C)/106 cells, respectively, at 3 x 10-4 m]. That the 7-11, but not the 1-7, amino acid fragment of SP caused superoxide production, suggested the effects of SP were receptor mediated. Eosinophils from hypersensitive ponies produced more superoxide in response to SP, but not phorbol myristate acetate or histamine, over the concentration range tested when compared with cells from normal ponies. The data obtained in this study suggest that although SP can directly activate equine eosinophils, in view of the high concentrations required, such actions may be of less relevance physiologically than other SP-mediated effects.

Foster, A. P., & Cunningham, F. M. (2003). Substance P induces activation, adherence and migration of equine eosinophils. Journal of veterinary pharmacology and therapeutics, 26(2), 131-138.

We found that substance P (SP) and calcitonin gene-related peptide (CGRP) (0.3-1 microM) increased, in a concentration-dependent manner, the basal secretion of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF alpha) from cultured lymphocyte-enriched mononuclear cells isolated from human peripheral blood. SP and CGRP (0.1 microM) synergistically increased basal TNF alpha secretion. Dynorphin A((1-17)) (0.1-1 microM) did not modify basal cytokine secretion. Lipopolysaccharide (10 ng/ml)-induced cytokine secretion and [(3)H]thymidine uptake were not altered by any neuropeptide (at 0.1 microM). Thus, SP and CGRP stimulate the production of pro-inflammatory cytokines from lymphocytes only at high concentrations, similar to those reached during tissue damage.

Cuesta, M. C., Quintero, L., Pons, H., & Suarez-Roca, H. (2002). Substance P and calcitonin gene-related peptide increase IL-1β, IL-6 and TNFα secretion from human peripheral blood mononuclear cells. Neurochemistry international, 40(4), 301-306.